The p.Gln530Ter-KCNQ1 variant was associated with a significantly older age at first cardiac event compared to other KCNQ1 pathogenic variants (44 vs 31 years, p=0.02).
Cohort (n=1,050)
Yes
Does the p.Gln530Ter-KCNQ1 variant alter the risk and onset age of cardiac events compared to other KCNQ1 pathogenic variants and controls in patients with Long QT syndrome?
The p.Gln530Ter-KCNQ1 variant is associated with a milder phenotype and later onset of cardiac events compared to other KCNQ1 pathogenic variants, highlighting the need for variant-specific risk assessment and long-term follow-up.
Absolute Event Rate: 44% vs 31%
p-value: p=0.02
Background: Variants in the KCNQ1 underlie the Long QT syndrome (LQTS) type 1.The clinical manifestations are influenced by the specific KCNQ1 pathogenic variant. Objective:We aimed to describe the phenotype in patients found to possess the p.Gln530Ter-KCNQ1 pathogenic variant common in Scandinavian LQTS patients.Methods: Clinical characteristics of p.Gln530Ter-KCNQ1variant patients from six university hospital registries in Sweden, Denmark, Norway, and USA were compared to carriers of other KCNQ1 pathogenic variants (non-p.Gln530Ter-KCNQ1) and gene-negative controls.Cardiac events (CE) encompassed syncope of unknown origin and ventricular arrhythmias (VA, episodes of torsades de pointes, appropriate ICD shocks, aborted cardiac arrest, or sudden cardiac death).Results: The p.Gln530Ter-KCNQ1 and non-p.Gln530Ter-KCNQ1 and control groups included 139 (65% female, 24% probands, mean age at end of follow-up 5120 years), 194 (65% female; mean age 4419), and 717 individuals (55% female; mean age 3924), respectively.CEs by the age of 60 were reported in: 30 (22%; of those 5 VA, all non-fatal) of p.Gln530Ter-KCNQ1; 46 (24%; 4 VA, all non-fatal) of non-p.Gln530Ter-KCNQ1; 81(11%; no VA) of controls.In p.Gln530Ter-KCNQ1 CE occurred at a significantly older age then in non-p.Gln530Ter-KCNQ1 (4422 vs.3122,p=0.02).Before age 30, CE risk in p.Gln530Ter-KCNQ1 did not differ from in controls (HRadj 1.1195% CI 0.65-1.89p=0.707), and was significantly lower than in non-p.Gln530Ter-KCNQ1.After age 30, CE risk in p.Gln530Ter-KCNQ1increased significantly (HRadj 3.2195%CI 1.49-6.92,p=0.003,compared to controls), and did not differ from non-p.Gln530Ter-KCNQ1. Conclusion:The p.Gln530Ter-KCNQ1variant is associated with later onset of CE as compared to other KCNQ1 pathogenic variants.
Savelev et al. (Sun,) conducted a cohort in Long QT syndrome (LQTS) type 1 (n=1,050). p.Gln530Ter-KCNQ1 pathogenic variant vs. Other KCNQ1 pathogenic variants and gene-negative controls was evaluated on Age at first cardiac event (years) (p=0.02). The p.Gln530Ter-KCNQ1 variant was associated with a significantly older age at first cardiac event compared to other KCNQ1 pathogenic variants (44 vs 31 years, p=0.02).